Post-Transcriptional Regulation of Tissue Regeneration by RNP-Granules

About This Grant

Project Summary P-bodies are ribonucleoprotein granules that form membraneless compartments through liquid-liquid phase separation and regulate gene expression by directing mRNAs for degradation, translation, or storage. In humans, P-bodies are estimated to influence one-third of genes in the genome. Recent research highlights their involvement in stem cells, where they regulate cell cycling and cell fate decisions. Despite these advances, little is known about how P-bodies function in connective tissue or during tissue regeneration. Our recent work using in vivo proximity labeling in zebrafish identified Ddx61, a protein central to P-body formation, as critical during regeneration. Ddx61 forms condensates reminiscent of P-bodies, and its loss is associated with reduced cell proliferation and impaired tissue regeneration. Interestingly, these regenerative P-bodies form in response to injury and dissipate once regeneration is complete, suggesting they are dynamically regulated. These findings provide a strong foundation to explore the mechanisms of P-body formation and their functional significance in regeneration. In my newly established laboratory, we aim to address the mechanisms underlying P-body formation and function in the context of tissue regeneration. Specifically, we will determine the composition of regenerative P-bodies using innovative tools, including in vivo proximity labeling and super-resolution microscopy. To establish causality, we will bioengineer artificial P-bodies and test their ability to regulate mRNA fate in zebrafish. This will be one of the first comprehensive studies on the post-transcriptional regulation of gene expression by P-bodies in connective tissue and during tissue regeneration. By uncovering how regenerative P-bodies regulate cell division and differentiation, this research will advance our understanding of post-transcriptional regulation and provide a foundation for developing novel therapeutic strategies for tissue regeneration, aging, and cancer.